Immunological Risk and Complement Genetic Evaluations in Early Onset De Novo Thrombotic Microangiopathy After Living Donor Kidney Transplantation: A Japanese Multicenter Registry

Overview

Journal Clin Exp Nephrol

Publisher Springer

Specialty Nephrology

Date 2023 Aug 27

PMID 37634218

Authors

Nobuhiro Fujiyama

Masayuki Tasaki

Hiroshi Harada

Koichi Tsutahara

Akihiko Matsumoto

Yuji Kamijo

Mariko Toyoda

Daiki Iwami

Masashi Inui

Hiroki Shirakawa

Jun Sugimura

Mitsuru Saito

Kiyohiko Hotta

Masayoshi Okumi

Kazuhide Saito

Yoshihiko Watarai

Yoshihiko Hidaka

Katsuki Ohtani

Norimitsu Inoue

Nobutaka Wakamiya

Tomonori Habuchi

Shigeru Satoh

Affiliations

Soon will be listed here.

Abstract

Background: Thrombotic microangiopathy (TMA) after kidney transplantation (KTx), particularly early onset de novo (dn) TMA, requires immediate interventions to prevent irreversible organ damage. This multicenter study was performed to investigate the allogeneic clinical factors and complement genetic background of dnTMA after KTx.

Methods: Perioperative dnTMA after KTx within 1 week after KTx were diagnosed based on pathological or/and hematological criteria at each center, and their immunological backgrounds were researched. Twelve aHUS-related gene variants were examined in dnTMA cases.

Results: Seventeen recipients (15 donors) were enrolled, and all dnTMA cases were onset within 72-h of KTx, and 16 of 17 cases were ABO incompatible. The implementation rate of pre-transplant plasmaphereses therapies were low, including cases with high titers of anti-A/anti-B antibodies. Examination of aHUS-related gene variants revealed some deletions and variants with minor allele frequency (MAF) in Japan or East Asian genome databases in genes encoding alternative pathways and complement regulatory factors. These variants was positive in 8 cases, 6 of which were positive in both recipient and donor, but only in one graft loss case.

Conclusions: Although some immunological risks were found for dnTMA after KTx, only a few cases developed into TMA. The characteristic variations revealed in the present study may be novel candidates related to dnTMA in Japanese or Asian patients, but not pathogenic variants of aHUS. Future studies on genetic and antigenic factors are needed to identify factors contributing to dnTMA after KTx.

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